The overall objective of this research program is to understand how steroid hormones, in conjunction with their receptor proteins, modulate the concentration of specific gene products (messenger RNA). An important goal for the next year is to carry out experiments that will elucidate whether steroid receptors act by controlling mRNA transcription of mRNA porcessing. The outcome of these experiments will determine to a large extent the direction of future work on steroid hormone action. A longer term goal is to know the spacial relationship of steroid receptors to the genes they regulate. To do this we will pursue two basic approaches. One approach will be to develop methods for direct visualization by electron microscopy of active transcription units and steroid receptors. This will require methods for spreading chromatin to observe nascent RNA fibrils and methods for tagging steroid receptors to make them visible by microscopy. The other approach will be to isolate and clone a specific gene that is known to be regulated by steroids with the eventual goal being to physically and chemically map the steroid receptor binding site, RNA polymerase promotor site, and the structural gene. We believe that these approaches will lead to a better understanding of the molecular connection between steroid receptors and gene action. BIBLIOGRAPHIC REFERENCES: Palmiter, R.D. (1975) Quantitation of Parameters that Determine the Rate of Ovalbumin Synthesis. Cell 4, 189-197.